We propose a multidisciplinary study of neural and neurohumoral regulation of lungs and airways, using techniques of cell biology, ultrastructure, physiology, pharmacology, immunology, and clinical investigation. Animal studies will examine sensory and motor pathways of cardiopulmonary nerves and carotid bodies, their central medullary connections efferent nerves, reflex organ responses (control of breathing, airway secretions, bronchomotor tone), and cellular responses (regulation of smooth muscle, mast cells, mucus glands, ion transport and cyclic AMP and GMP). Dr. Basbaum (D-1) will utilize morphologic techniques to study sensory and motor nerves in airways, collaborating with Dr. Sampson (D-2), who will perform neurophysiological studies of these structures, as well as studies on isolated smooth muscle cells. Dr. Nadel (D-3) will study effects of airway epithelial damage on the autonomic control of airways and breathing. Drs. Coleridge and Coleridge (D-4) will perform neurophysiologic studies on cardiopulmonary sensory nerves. Drs. McDonald and Mitchell (D-5) will utilize morphologic and neurophysiologic techniques to study carotid body regulation and to locate its central connections. Dr. Gold (D-6) will study interactions betweeen mast cells, mediators and nerves in experimental canine anaphylaxis. Drs. Nadel, Davis, and Widdicombe (D-7) will examine autonomic regulation of mucus secretion and ion transport in airways. Clinical investigation will aim to relate the animal studies in humans in health and disease, and to develop specific and sensitive tests for early detection of disease. Dr. Boushey (E-1) will study mechanisms underlying exaggerated bronchial responses to inhaled agents. Dr. Gold (E-2) will correlate physiologic tests developed for early detection of disease with anatomic studies.